Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

GH has been implicated in the pathophysiology of various acute and chronic complications of diabetes mellitus. As a consequence, there has been a great deal of interest in developing methods for suppressing GH secretion in diabetes. SMS 201-995 is a long-acting somatostatin analog which inhibits the secretion of numerous hormones, including GH. To determine the metabolic and hormonal responses to SMS 201-995 independent of endogenous insulin suppression, we studied six patients with insulin-dependent diabetes mellitus while they received 150 micrograms SMS 201-995, sc, daily for an 8-week period. This treatment resulted in no change in 24-h glucose profiles, although the mean insulin dose decreased by 19%, while hemoglobin A1c decreased significantly (0.084 +/- 0.023 to 0.067 +/- 0.011, P = 0.04). The 24-h profiles of blood lactate, plasma free insulin, glucagon, FFA, blood glycerol, and beta-hydroxybutyrate were unchanged, whereas that of blood alanine increased significantly (7.8 +/- 0.4 to 10.6 +/- 0.9 mmol/L.h; P = 0.01). GH secretion declined in five of the six patients; the mean values before and during SMS 201-995 treatment were 102 +/- 23 and 68 +/- 12 micrograms/L.h, respectively (P = NS), for the six patients. [In the five patients in whom GH secretion declined, the mean values before and during SMS 201-995 treatment were 115 +/- 23 and 63 +/- 14 micrograms/L.h, respectively (P = 0.01).] These results suggest that SMS 201-995 may be administered to patients with insulin-dependent diabetes mellitus without a deleterious effect on metabolic control.
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PMID:The effects of SMS 201-995 (sandostatin) on metabolic profiles in insulin-dependent diabetes mellitus. 264 88

We have examined the effect of glucose and FFA on GH-releasing factor (GHRF)-mediated GH secretion in rats under pentobarbital anesthesia. Hyperglycemia did not affect GH secretion induced by administration of 20, 100, and 200 ng GHRF/100 g body weight. In contrast, GH response to 50 ng GHRF/100 g body weight in lipid heparin-treated rats, which showed high plasma FFA levels, was significantly suppressed compared with the control group (plasma peak GH: control, 1526 +/- 263 ng/ml; lipid-heparin group, 377 +/- 69 ng/ml P less than 0.05, mean +/- SEM). This suppressive effect of FFA on GH secretion was abolished by pretreatment with antisomatostatin serum (ASS) (GH level at 4 min after GHRF administration: ASS-saline group, 1606 +/- 210 ng/ml; ASS-lipid-heparin group, 1531 +/- 174 ng/ml; mean +/- SEM). These results suggest that hyperglycemia does not change the GH response to GHRF and that elevation of plasma FFA suppresses GHRF-induced GH secretion by the stimulation of somatostatin secretion in rats.
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PMID:The effect of glucose and free fatty acids on growth hormone (GH)-releasing factor-mediated GH secretion in rats. 287 Sep 16

We studied the influence of hyperglycemia on glucose homeostasis in man by determining the effect of graded hyperglycemia on peripheral glucose uptake and systemic metabolism in the presence of basal and increased serum insulin concentrations in 10 normal men. This was achieved by the simultaneous application of forearm and clamp techniques (euglycemic and hyperglycemic) during the combined iv infusion of somatostatin, glucagon, and insulin. While mean (+/- SE) basal serum insulin levels (14 +/- 2 microU/ml) were maintained, the elevation of fasting arterial glucose concentrations (90 +/- 1 mg/dl) to 146 +/- 1 and 202 +/- 1 mg/dl (each for 120 min) increased forearm glucose uptake (FGU) only modestly from 0.06 +/- 0.01 to 0.15 +/- 0.02 and then to 0.24 +/- 0.03 mg/100 ml forearm X min, respectively. During physiological hyperinsulinemia (47 +/- 3 microU/ml), the influence of similar graded hyperglycemia on FGU was considerably enhanced. At plasma glucose concentrations of 90 +/- 1, 139 +/- 1, and 206 +/- 1 mg/dl, FGU rose to 0.33 +/- 0.05, 0.59 +/- 0.07, and 0.83 +/- 0.12 mg/100 ml forearm X min, respectively. The glucose infusion rate required to maintain the glucose clamp with basal insulin levels was 1.08 +/- 0.20 and 2.67 +/- 0.39 mg/kg X min at glucose concentrations of 146 +/- 1 and 202 +/- 1 mg/dl, respectively. During physiological hyperinsulinemia, however, the glucose infusion rate required was 4.15 +/- 0.39, 9.45 +/- 1.05, and 12.70 +/- 0.81 mg/kg X min at glucose levels of 90 +/- 1, 139 +/- 1, and 206 +/- 1 mg/dl, respectively. Lactate concentrations rose significantly during hyperglycemia, but the rise in the presence of increased insulin concentrations (from 0.72 +/- 0.06 to 1.31 +/- 0.11 mmol/liter; P less than 0.001) considerably exceeded the increment (from 0.74 +/- 0.05 to 0.92 +/- 0.03 mmol/liter) with basal insulin levels. While both FFA and glycerol concentrations were immediately reduced by euglycemic hyperinsulinemia, the fall in FFA during hyperglycemia in the presence of basal insulin levels preceded the decrease in glycerol concentrations by 45 min. Forearm oxygen consumption did not change throughout the study.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The influence of graded hyperglycemia with and without physiological hyperinsulinemia on forearm glucose uptake and other metabolic responses in man. 287 53

We have used primed constant infusions of [1-13C]palmitic acid, [2-3H]glycerol, and [U-14C]glucose to evaluate the response of glucose and fat kinetics to alpha or beta adrenergic blockade in conscious dogs. The response of each blocking agent was evaluated both with and without control of the glucoregulatory hormones. When hormones were controlled, somatostatin and metyrapone were infused to block hormonal secretion, and insulin, glucagon, growth hormone, and cortisol were replaced at basal physiological rates. alpha blockade (beta stimulation) did not influence glucose production or oxidation, but it did decrease glucose clearance when hormones were controlled. Clearance did not decrease during blockade when hormones were not controlled, presumably because of the resulting increase in the plasma insulin concentration. Glucose production, plasma glucose concentration, and glucose oxidation all increased with beta blockade (alpha stimulation). alpha blockade (beta stimulation) resulted in an increase in lipolysis, whereas beta blockade (alpha stimulation) resulted in a decrease in lipolysis. In neither case, however, did FFA oxidation change. We conclude that (a) the predominant effect of unopposed stimulation is the stimulation of lipolysis, whereas unopposed alpha stimulation inhibits lipolysis. Direct effects of either alpha or beta stimulation on glucose kinetics are less dramatic, but both alpha and beta stimulation decrease glucose clearance.
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PMID:The integrated effect of adrenergic blockade on glucose, fatty acid, and glycerol kinetics: responses in the basal state and during hormonal control with somatostatin-hormonal infusion. 288 Oct 26

The treatment of acromegaly is not optimal at present, since many patients have continued growth hormone hypersecretion. We report the acute effects of a cyclic octapeptide analogue of somatostatin, SMS 201-995 (Sandoz) in 9 nondiabetic, acromegalic patients between the ages of 30 and 74. We report potent and prolonged dose-dependent effects to suppress growth hormone secretion. A single 50 micrograms dose of SMS 201-995 inhibited growth hormone concentration rapidly within 15 minutes, with maximal effect in 75 minutes. Maximal inhibition was of the order of 80%, with absolute concentrations under 2 micrograms/L for about 6 hours in 5 of 7 patients. Growth hormone concentrations remained significantly suppressed below placebo control for up to 24 hours after a single dose of SMS 201-995, but the inhibitory effects on insulin and C-peptide concentrations were limited to 2 hours. The effects on glucagon secretion were minimal, and also evident for only 2 hours. Mild transient postprandial elevations of plasma glucose and FFA were documented. No adverse effects were noted; routine hematology, biochemistry, and vital signs were not altered. Thus SMS 201-995, with preferential effects at the pituitary somatotroph, holds considerable promise as an attractive and viable alternative for treatment of acromegaly.
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PMID:The somatostatin analogue SMS 201-995 in acromegaly: prolonged, preferential suppression of growth hormone but not pancreatic hormones. 288 54

Although fasting decreases insulin-mediated glucose uptake (IMGU), its effect on noninsulin-mediated glucose uptake (NIMGU) is not known. To examine this issue we studied seven obese men [mean (+/- SD) age, 36 +/- 5 yr; weight, 91 +/- 13 kg] after an overnight fast (day 0) and 3 days (day 4) and 9 days (day 10) of total fasting and six normal weight men (age, 32 +/- 4 yr; weight, 73 +/- 6 kg) after an overnight and 3 days of fasting. To study NIMGU, somatostatin (0.16 micrograms/kg.min) was infused to create severe insulin deficiency and [3H]3-glucose to measure glucose disappearance (Rd), while serum glucose was sequentially clamped at a level of about 4.7 mmol/L for 180 min and about 11 mmol/L for an additional 100 min. The results from the last 60 min of each glycemic plateau were used for analysis. Under these conditions insulin action is absent and Rd = NIMGU. Since under conditions of euglycemic insulinopenia, NIMGU into noncentral nervous system tissues is negligible, and central nervous system (CNS) glucose uptake saturates at physiological glucose concentrations, it follows that at a glucose level of about 4.7 mmol/L, NIMGU reflects CNS glucose uptake and at about 11 mmol/L, NIMGU reflect CNS plus non-CNS tissues. Thus, non-CNS NIMGU = NIMGU at 11 mmol/L - NIMGU at about 4.7 mmol/L. The obese subjects' mean weight fell to 88 +/- 5 kg on day 4 and 85 +/- 5 kg on day 10 (P less than 0.001 between all values). The mean basal serum glucose level fell from 5.3 +/- 0.1 on day 0 to 4.2 +/- 0.2 and 3.8 +/- 0.2 mmol/L on days 4 and 10, respectively (P less than 0.01 between all values). During insulinopenia plasma FFA and serum beta-hydroxybutyrate levels on day 10 were 3- and 30-fold higher than the basal prefast levels, respectively. Noninsulin-mediated glucose clearance at about 4.7 mmol/L did not change during fasting [0.0016 +/- 0.0001 (day 0) vs. 0.0016 +/- 0.0001 (day 4) and 0.0014 +/- 0.0001 L/kg.min (day 10); P = NS between all values]; at about 11 mmol/L noninsulin-mediated glucose clearance fell from 0.0016 +/- 0.0001 on day 0 to 0.0001 +/- 0.0001 dL/kg.min on day 10 (P less than 0.001). Results in the lean group were similar to those in the obese group after a 3-day fast.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Fasting decreases rates of noninsulin-mediated glucose uptake in man. 304 43

This study was done to compare the actions of pulsatile and continuous insulin administration in eight noninsulin-dependent diabetic patients. Human insulin was delivered in a pulsatile manner (1.3 mU/kg.min for 2 min, followed by 11 min during which no insulin was infused) or continuously (0.2 mU/kg.min) for 325 min. Endogenous hormone secretion was inhibited by somatostatin (125 micrograms/h), and glucagon was replaced at rate of 3.5 micrograms/h. Under these conditions plasma C-peptide levels fell progressively to extremely low values at the end of the experiment. Continuous insulin infusion resulted in steady plasma insulin levels, averaging 86 pmol/L, while during intermittent insulin administration plasma insulin levels were 5.7 and 158 pmol/L before and 3 min after the start of the insulin injection, respectively. Basal plasma glucagon [mean 158 +/- 11 (+/- SE) vs. 163 +/- 21 ng/L; P = NS] levels were similar on both occasions. During replacement peripheral plasma glucagon levels were no different whatever the mode of insulin administration, nor did they differ from the basal values. The mean plasma glucose concentrations were similar before both studies and rose to 9.5 and 8.6 mmol/L in the first 65 min during continuous and pulsatile insulin administration, respectively. In contrast, during the last 65 min, plasma glucose averaged 6.2 mmol/L during both studies. The glucose infusion rate initially increased, but then rapidly fell to values close to zero at the end of the first 65 min during the continuous insulin infusion, whereas during this time it averaged 0.59 +/- 0.10 mg/kg.min (32.5 +/- 5.5 mumol/kg.min) during pulsatile insulin administration. In the last 65 min the glucose infusion rate was significantly higher during pulsatile than during continuous insulin delivery. Furthermore, pulsatile rather than continuous insulin administration significantly reduced plasma triglyceride, very low density lipoprotein triglyceride, and FFA levels and increased high density lipoprotein cholesterol and apolipoprotein-B levels. We conclude that pulsatile insulin delivery has advantageous metabolic effects compared to continuous hormone administration in patients with noninsulin-dependent diabetes mellitus.
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PMID:Advantageous metabolic effects of pulsatile insulin delivery in noninsulin-dependent diabetic patients. 305 47

Recent studies have established the existence of substrate cycles in humans, but factors regulating the rate of cycling have not been identified. We have therefore investigated the acute response of glucose/glucose-6P-glucose (glucose) and triglyceride/fatty acid (TG/FA) substrate cycling to the infusion of epinephrine (0.03 microgram/kg.min) and glucagon. The response to a high dose glucagon infusion (2 micrograms/kg.min) was tested, as well as the response to a low dose infusion (5 ng/kg.min), with and without the simultaneous infusion of somatostatin (0.1 microgram/kg.min) and insulin (0.1 mU/kg.min). Additionally, the response to chronic prednisone (50 mg/d) was evaluated, both alone and during glucagon (low dose) and epinephrine infusion. Finally, the response to hyperglycemia, with insulin and glucagon held constant by somatostatin infusion and constant replacement of glucagon and insulin at basal rates, was investigated. Glucose cycling was calculated as the difference between the rate of appearance (Ra) of glucose as determined using 2-d1- and 6,6-d2-glucose as tracers. TG/FA cycling was calculated by first determining the Ra glycerol with d5-glycerol and the Ra FFA with [1-13C]palmitate, then subtracting Ra FFA from three times Ra glycerol. The results indicate that glucagon stimulates glucose cycling, and this stimulatory effect is augmented when the insulin response to glucagon infusion is blocked. Glucagon had minimal effect on TG/FA cycling. In contrast, epinephrine stimulated TG/FA cycling, but affected glucose cycling minimally. Prednisone had no direct effect on either glucose or TG/FA cycling, but blunted the stimulatory effect of glucagon on glucose cycling. Hyperglycemia, per se, had no direct effect on glucose or TG/FA cycling. Calculations revealed that stimulation of TG/FA cycling theoretically amplified the sensitivity of control of fatty acid flux, but no such amplification was evident as a result of the stimulation of glucose cycling by glucagon.
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PMID:Hormonal control of substrate cycling in humans. 328 15

This study was undertaken to elucidate the mechanism(s) involved in glucocorticoid-induced insulin antagonism. Male Sprague-Dawley rats (200 to 210 g) were injected with 1 mg/kg dexamethasone-phosphate (Dex) or the vehicle every other day for 10 days. Two days after the last injection, fasted anesthetized animals were infused (per kg body weight per min) with 8 mg glucose, 5 mU porcine insulin and 1.4 micrograms somatostatin with blood sampling before, and at 10 min intervals between 90 and 130 min after the pancreatic suppression test was begun. At the end of the test, abdominal muscle was quickly freeze-clamped and the substrate and products of the rate-determining reactions of glycolysis and glycogenesis were measured. Dex-treated rats had higher basal (0 min) and steady-state levels (90-130 min) of both glucose and insulin signifying insulin antagonism. The pattern of muscle tissue metabolites revealed no free intracellular glucose in either group and concentrations of all other metabolites in the Dex-treated rats were less than those in the control animals (except for a small increase in glycogen). These results suggest a site of insulin antagonism between (and including) insulin binding and glucose transport. Further studies in the Dex-treated rats revealed normal: a) insulin binding to freshly isolated hepatocytes; b) basal and insulin-stimulated xylose transport in soleus muscle; c) basal and insulin-stimulated glucose uptake in hemidiaphragms. These normal in-vitro results suggested that a circulating factor may be responsible. Repeat pancreatic suppression tests in the Dex-treated rats revealed blunted suppression of serum FFA concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Possible role for the glucose-fatty acid cycle in dexamethasone-induced insulin antagonism in rats. 330 80

We have determined peripheral venous somatostatin like immunoreactivity (SLI) levels in 11 normal subjects (blood glucose--BG--: 4.4 +/- 0.1 mM; ketone bodies--KB--: 90 +/- 12 microM; plasma free fatty acids--FFA --: 340 +/- 42 microM), 4 Biostator controlled insulin dependent diabetics (BG: 5.4 +/- 0.2 mM; FFA: 418 +/- 38 microM; KB: 226 +/- 41 microM) and 7 poorly controlled ketotic diabetics (BG: 10.8 +/- 1.3 mM; FFA: 915 +/- 19 microM; KB: 2490 +/- 576 microM). SLI was determined again after 48 to 96 hours of intravenous insulin infusion for the 7 ketotic diabetics and after transient interruption of insulin infusion for the Biostator controlled diabetics. Relative to normal subjects ketotic diabetics had elevated SLI levels (29.7 +/- 5.9 vs 13.5 +/- 1.8 ng/L, p less than 0.01) whereas biostator-controlled patient had near to normal values (20.4 +/- 6.4 ng/L, p greater than 0.30). Transient arrest of insulin infusion in the Biostator controlled diabetics resulted only in a mild metabolic deterioration (BG: 12.8 +/- 2.1 mM; FFA: 640 +/- 146 microM; KB: 950 +/- 163 microM) without a significant rise of SLI. Intravenous insulin infusion in the initially ketotic patients decreased BG and KB in each subject (p less than 0.01) but decreased FFA (1097 +/- 170 to 453 +/- 74 microM, p less than 0.05) and SLI (34.0 +/- 12.0 to 9.8 +/- 2.4 ng/L, p less than 0.05) only in 4 patients whereas both FFA (737 +/- 107 to 725 +/- 25 microM) and SLI (27.6 +/- 4.7 to 20.3 +/- 4.7 ng/L) levels remained stable in the other 3. These results suggest that SLI levels in type I diabetics are dependent the degree of metabolic control and could be related to the variations of FFA concentrations.
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PMID:Regulation of peripheral plasma somatostatin like immunoreactivity in type I diabetes: role of the degree of metabolic control. 351 50


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